GRHL2 grainyhead like transcription factor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRHL2provided by HGNC
Official Full Name: grainyhead like transcription factor 2provided by HGNC
Primary source: HGNC:HGNC:2799
See related: Ensembl:ENSG00000083307 MIM:608576
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BOM; ECTDS; PPCD4; DFNA28; TFCP2L3
Summary: The protein encoded by this gene is a transcription factor that can act as a homodimer or as a heterodimer with either GRHL1 or GRHL3. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal dominant type 28 (DFNA28).[provided by RefSeq, Mar 2009]
Expression: Broad expression in skin (RPKM 14.0), prostate (RPKM 13.5) and 14 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 8q22.3

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	8	NC_000008.11 (101492439..101678104)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (102504668..102681954)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Whole-genome sequencing identified a unique variant (c.20+544G>T) within an intronic regulatory region of GRHL2.
Title: Ectopic GRHL2 Expression Due to Non-coding Mutations Promotes Cell State Transition and Causes Posterior Polymorphous Corneal Dystrophy 4.
GRHL2 gene may have a role in orbital innervations and the defect in this gene (deletion) may be related to the Congenital fibrosis of the extraocular muscles type 1 phenotype.
Title: A microdeletion in the GRHL2 Gene in two unrelated patients with congenital fibrosis of the extra ocular muscles.
In this study, we demonstrated for the first time that GRHL2 has a functional role in the regulation of epithelial plasticity of PDAC cells.
Title: Grainyhead-like 2 (GRHL2) regulates epithelial plasticity in pancreatic cancer progression.
data analysis and modeling results highlight the relationships among multiple crucial Epithelial-to-Mesenchymal Transition /Mesenchymal-to-Epithelial Transition drivers including ZEB1, GRHL2, CD24, and ESRP1, particularly in basal-like breast cancers, which are most similar to triple-negative breast cancer (TNBC) and are considered the most dangerous subtype
Title: The GRHL2/ZEB Feedback Loop-A Key Axis in the Regulation of EMT in Breast Cancer.
Data indicate a 'phenotypic stability factors' (PSFs) such as GRHL2 that couple to the core epithelial-to-mesenchymal transition (EMT) decision-making circuit (miR-200/ZEB) and stabilize hybrid epithelial/mesenchymal (hybrid E/M) E/M phenotype.
Title: Stability of the hybrid epithelial/mesenchymal phenotype.
All of these processes involve epithelial-mesencyhmal transition (EMT), MET or a sequence of both, suggesting that the GRHL factors((GRHL1, GRHL2 and GRHL3), could potentially affect tumor initiation and progression via EMT
Title: Roles of Grainyhead-like transcription factors in cancer.
Silencing of GRHL2 expression in non-tumorigenic kidney cell line results in increased cell proliferation, increased resistance to apoptosis, as well as changes in the levels of selected proteins involved in the pathogenesis of clear cell renal cell carcinoma (ccRCC). These changes support the potential role for GRHL2 as a suppressor of ccRCC.
Title: Potential protective role of Grainyhead-like genes in the development of clear cell renal cell carcinoma.
Results demonstrate a mechanistic role for GRHL2 in promoting anoikis through metabolic alterations.
Title: Grainyhead-like 2 Reverses the Metabolic Changes Induced by the Oncogenic Epithelial-Mesenchymal Transition: Effects on Anoikis.
GRHL2 maintained AR expression in multiple prostate cancer model systems, was required for cell proliferation, enhanced AR's transcriptional activity, and colocated with AR at specific sites on chromatin to regulate genes relevant to disease progression.
Title: Novel Androgen Receptor Coregulator GRHL2 Exerts Both Oncogenic and Antimetastatic Functions in Prostate Cancer.
Studies indicate that Grainyhead-like transcription factor 2 (GRHL2) controls the expression of E-cadherin (CDH1) required for adherens junctions and possibly regulates the expression of claudin-4 (CLDN4) in tight junctions.
Title: Transcriptional mechanisms coordinating tight junction assembly during epithelial differentiation.

Submit: New GeneRIF Correction See all GeneRIFs (44)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
CORNEAL DYSTROPHY, POSTERIOR POLYMORPHOUS, 4 MedGen: CN248531 OMIM: 618031 GeneReviews: Not available	not available
Deafness, autosomal dominant 28 MedGen: C1837640 OMIM: 608641 GeneReviews: Hereditary Hearing Loss and Deafness Overview	Compare labs
Ectodermal dysplasia/short stature syndrome MedGen: C4014987 OMIM: 616029 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study (GWAS) for bronchopulmonary dysplasia. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

Go to the top of the page Help

Endoderm Differentiation, organism-specific biosystem (from WikiPathways)
Endoderm Differentiation, organism-specific biosystemModel depicting endoderm specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell lin...
Mesodermal Commitment Pathway, organism-specific biosystem (from WikiPathways)
Mesodermal Commitment Pathway, organism-specific biosystemModel depicting mesodermal specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell l...

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH36161 (e-PCR)
- UniSTS:65903

RH123420 (e-PCR)
- UniSTS:135795

WI-11745 (e-PCR)
- UniSTS:82820

RH65468 (e-PCR)
- UniSTS:46301

Homology

Homologs of the GRHL2 gene: The GRHL2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 229 organisms have orthologs with human gene GRHL2
Orthologs

Clone Names

FLJ11172, FLJ13782, MGC149294, MGC149295

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
DNA-binding transcription activator activity, RNA polymerase II-specific	IMP Inferred from Mutant Phenotype more info	PubMed
DNA-binding transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	ISM Inferred from Sequence Model more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
chromatin DNA binding	IDA Inferred from Direct Assay more info	PubMed
intronic transcription regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
bicellular tight junction assembly	IMP Inferred from Mutant Phenotype more info	PubMed
brain development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
camera-type eye development	IEA Inferred from Electronic Annotation more info
cardiac ventricle morphogenesis	IEA Inferred from Electronic Annotation more info
cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
cell junction assembly	IMP Inferred from Mutant Phenotype more info	PubMed
cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
embryonic cranial skeleton morphogenesis	IEA Inferred from Electronic Annotation more info
embryonic digit morphogenesis	IEA Inferred from Electronic Annotation more info
epidermis development	IDA Inferred from Direct Assay more info	PubMed
epithelial cell morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
epithelial cell morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
epithelial cell morphogenesis involved in placental branching	IEA Inferred from Electronic Annotation more info
epithelium migration	ISS Inferred from Sequence or Structural Similarity more info
face development	IEA Inferred from Electronic Annotation more info
lung epithelial cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
lung lobe morphogenesis	IEA Inferred from Electronic Annotation more info
multicellular organism growth	IEA Inferred from Electronic Annotation more info
negative regulation of keratinocyte differentiation	IDA Inferred from Direct Assay more info	PubMed
neural tube closure	ISS Inferred from Sequence or Structural Similarity more info
neural tube development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of telomerase activity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
regulation of DNA methylation	IDA Inferred from Direct Assay more info	PubMed
regulation of DNA methylation	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
cell-cell junction	IDA Inferred from Direct Assay more info	PubMed
membrane	IEA Inferred from Electronic Annotation more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: grainyhead-like protein 2 homolog

Names: brother of mammalian grainyhead; grainyhead-like 2; transcription factor CP2-like 3

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011971.2 RefSeqGene

Range

5001..182287

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001330593.1 → NP_001317522.1 grainyhead-like protein 2 homolog isoform 2

Status: REVIEWED

Source sequence(s)

AK296817, AP000426, AP001207, BC069633, BX117477, DN916458

Consensus CDS

CCDS83312.1

UniProtKB/Swiss-Prot

Q6ISB3

UniProtKB/TrEMBL

B4DL28

Related

ENSP00000379260.1, ENST00000395927.1

Conserved Domains (1) summary

pfam04516
Location:213 → 422

CP2; CP2 transcription factor
NM_024915.3 → NP_079191.2 grainyhead-like protein 2 homolog isoform 1

See identical proteins and their annotated locations for NP_079191.2

Status: REVIEWED

Source sequence(s)

AP000426, AP001207, BC069638

Consensus CDS

CCDS34931.1

UniProtKB/Swiss-Prot

Q6ISB3

Related

ENSP00000495564.1, ENST00000646743.1

Conserved Domains (1) summary

pfam04516
Location:229 → 438

CP2; CP2 transcription factor

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p12 Primary Assembly

Range

101492439..101678104

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011517307.3 → XP_011515609.1 grainyhead-like protein 2 homolog isoform X2

Conserved Domains (1) summary

pfam04516
Location:229 → 438

CP2; CP2 transcription factor
XM_011517306.3 → XP_011515608.1 grainyhead-like protein 2 homolog isoform X1

See identical proteins and their annotated locations for XP_011515608.1

UniProtKB/Swiss-Prot

Q6ISB3

Conserved Domains (1) summary

pfam04516
Location:213 → 422

CP2; CP2 transcription factor
XM_024447286.1 → XP_024303054.1 grainyhead-like protein 2 homolog isoform X3